The prevention of microbial infections and pathogenic processes via the use of vaccines is considered one of the most effective and desirable procedures to combat illness. Antigens or immunogens are introduced into an organism in a manner that stimulates an immune response in the host organism in advance of an infection or disease. Traditional vaccine strategies, however, have not been effective in mounting protection against many pathogens or cancers. Of more than 100 pathogens, only about 20 successful vaccines have been made by traditional vaccine strategies. Of those vaccines that induce a high cytotoxic T lymphocyte (CTL) response, some often show a modest objective response rate due to poor immunogenicity, immuno-avoidance mechanisms, and deceptive imprinting. Current methods of vaccine delivery have a modest success rate in terms of inducing protective immune responses because they do not induce robust “danger signals,” they initiate inhibitory responses that act as feedback mechanisms, and they deliver antigens to nonprofessional antigen presenting cells (APCs). Current cancer vaccines, for example, even when mounting a high CTL response, show a modest (2.6%) objective response rate. They are associated with a number of disadvantages, including poor immunogenicity and immuno-avoidance mechanisms. Moreover, the most promising cancer vaccines (dendritic cell-based and G-vax-based), are extremely costly and preparation of these vaccines is very involved (e.g., requiring personalization and GMP manufacturing).
Genetic vaccination or genetic immunization, which involves the inoculation of genetic materials into mammalian hosts to produce antigens, is considered a possible approach for vaccines including cancer vaccines. The delivered mammalian expression vector encoding the antigen of interest results in in vivo expression and subsequently to the development of antigen-specific responses. In addition, genes are negatively-charged polymers, which cannot cross cell membranes and reach the cell nucleus, where they can express a protein of interest. Genetic vaccination offers a number of advantages, including generation of a full spectrum of native epitopes expressed in vivo, achievement of the native conformation of a protein compared with administration of recombinant protein expressed in vitro, induction of antibody and cellular immune responses, and elimination of the need for costly and commonly challenging steps for antigen production. Genetic vaccination, however, is associated with a number of disadvantages including breaking tolerance to self antigens, poor in vivo delivery of nucleic acids into the cell and nucleus, a lack of specificity for particular types of cells, and weak immune responses.
Other forms of vaccines are associated with drawbacks as well. For example, viral delivery of genes results in strong immune responses to viral vectors and is associated with safety concerns. Protein purification from bacteria and production of peptides for use as antigens is expensive and time consuming.
Currently, there are no cost-effective, efficacious forms of vaccines that target APCs to produce specific and robust immune responses with no or few side effects. There is thus a significant need for a vaccine that targets professional APCs and elicits a strong and specific cellular and antibody response and that is safe, cost-effective and easy to use.